Study Reveals New Pathway To Stop Spread Of Brain Cancer

Researchers at UT Southwestern have identified a molecular pathway, which is responsible for the spread of glioblastoma cancer to surrounding tissue in the brain, and also an existing drug that curbed the tumor growth in animal models. The findings, published in Nature Cell Biology, have led to a clinical trial, which offers new hope to patients with glioblastoma. This is the most common form of brain cancer in adults, which kills many worldwide every year.

Despite years of research, the prognosis for most patients with glioblastoma remains grim, with a median survival after diagnosis of just 15-18 months. Part of the challenge in treating this cancer is its invasive nature as the glioblastoma tumors invade the surrounding healthy brain tissue, sending tentacle-like extensions out from the primary tumor, which are impossible to remove with surgery alone and difficult to be treated with chemotherapy.

Researchers have long considered the epidermal growth factor receptor or EGFR, a protein that sits on the surface of cells, as a driver of this cancer. In nearly half of glioblastoma patients, the gene that codes for EGFR is amplified, causing glioblastoma cells to produce far more molecular signals spurred by this protein and causing tumor cells to proliferate. Consequently, researchers add several clinical trials have focused on inhibiting EGFR but each failed to improve the prognosis for glioblastoma.

EGFR on glioblastoma cells can send these signals in two ways - either without prompting, a state known as constitutive signalling, or when stimulated with proteins called ligands. The differences between these two pathways have been considered inconsequential so glioblastoma patients with amplified EGFR have been grouped together in clinical trials.

In the new study, researchers from across the world showed that when cells with amplified EGFR were stimulated with ligands, this receptor appeared to act as a tumor suppressor, preventing invasion into healthy tissue both in laboratory and animal models. Further experiments showed that a cytoskeletal protein called BIN3 appears to be responsible for inhibiting this invasion. When the researchers dosed animals with amplified EGFR glioblastoma tumors with an FDA-approved arthritis drug called tofacitinib that increases the amount of EGFR ligands and BIN3, tumors remained smaller and were less likely to invade healthy brain tissue. Additionally, these animals survived significantly longer than animals that didn't receive this drug.

In conclusion, researchers said that these approaches could offer new tools in the fight against the deadly glioblastoma.

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